HISTAMINE H3 RECEPTOR ANTAGONIST: THERAPEUTIC POTENTIAL AS ANTINEOPLASTIC AGENTS WITH THE ABILITY TO OVERCOME CHEMORESISTANCEIN TRIPLE NEGATIVE BREAST CANCER

IGNACIO OSPITAL; MÓNICA A. TÁQUEZ DELGADO; MELISA B. NICOUD; MARIA BETINA COMBA; MARÍA MARTA ZANARDI; JOÃO P. S. FERNANDES; VANINA AS. MEDINA

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Biología (SAB), la Asociación Argentina de Farmacología Experimental (AAFE) y la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL)

Triple-negative breast cancer (TNBC) accounts for 10-15% of newly diagnosed cases of BC. It is recognized as the most aggressive subtype, carrying a particularly grim prognosis. Paclitaxel (PTX) is used as the standard of care. However, due to its limited solubility, secondary effects and the acquisition of chemoresistance, its application in the clinic has been challenged. Our earlier findings revealed the presence of the histamine H3 receptor (H3R) in human benign and malignant lesions, as well as in breast tissue derived cell lines. The aim of this work was to evaluate the expression of H3R particularly in TNBC samples. In addition, we aimed to discover whether novel H3R antagonists, LINS01022 and LINS01023, show antitumoral effects in murine 4T1 TNBC cells and if they could also potentiate PTX therapy, even in resistant cells (4T1R) in vitro and in vivo models. The H3R expression was assessed in 50 TNBC samples by immunohistochemistry evidencing a higher H3R expression in tumor samples when compared with peritumoral tissue. A high level of H3R was associated with poor overall survival in TNBC patients. Results indicate that both LINS01022 and LINS01023 produced significant inhibition on cell proliferation and viability, inducing cell apoptosis in 4T1 and 4T1R cells, potentiating PTX-induced effects (P